Antisense oligonucleotide modulation of STAT3 expression

Abstract

Compounds, compositions and methods are provided for inhibiting the expression of human STAT3. The compositions comprise antisense oligonucleotides targeted to nucleic acids encoding STAT3. Methods of using these oligonucleotides for inhibition of STAT3 expression and for promotion of apoptosis are provided. Methods for treatment of diseases, particularly inflammatory diseases and cancers, associated with overexpression or constitutive activation of STAT3 or insufficient apoptosis are also provided.

What is claimed is:  
     
       1. An antisense compound 20 to 30 nucleobases in length targeted to nucleobases 637-656 and 1669-1688 of human STAT3 (SEQ ID NO: 1), wherein said antisense compound inhibits the expression of human STAT3. 
     
     
       2. The antisense compound of  claim 1  which is an antisense oligonucleotide. 
     
     
       3. The antisense compound of  claim 2  wherein the antisense oligonucleotide comprises at least one modified internucleoside linkage. 
     
     
       4. The antisense compound of  claim 3  wherein the modified internucleoside linkage is a phosphorothioate linkage. 
     
     
       5. The antisense compound of  claim 2  wherein the antisense oligonucleotide comprises at least one modified sugar moiety. 
     
     
       6. The antisense compound of  claim 5  wherein the modified sugar moiety is a 2′-O-methoxyethyl moiety. 
     
     
       7. The antisense compound of  claim 2  wherein the antisense oligonucleotide comprises at least one modified nucleobase. 
     
     
       8. The antisense compound of  claim 7  wherein modified nucleobase is a 5-methyl cytosine. 
     
     
       9. The antisense compound of  claim 1  wherein the antisense oligonucleotide is a chimeric oligonucleotide. 
     
     
       10. A composition comprising the antisense compound of  claim 1  and a pharmaceutically acceptable carrier or diluent. 
     
     
       11. The composition of  claim 10  further comprising a colloidal dispersion system. 
     
     
       12. The composition of  claim 10  wherein the antisense compound is an antisense oligonucleotide. 
     
     
       13. A method of inhibiting the expression of STAT3 in human cells or tissues comprising contacting said cells or tissue in vitro or ex vitro with the antisense compound of  claim 1  so that expression of STAT3 is inhibited. 
     
     
       14. A method of inducing apoptosis in a cell comprising contacting a cell in vitro or ex vivo with the antisense compound of  claim 1  so that apoptosis is induced. 
     
     
       15. The method of  claim 14  wherein said apoptosis is Fas-mediated.